A selective reversible monoamine oxidase B inhibitor in smoking cessation: effects on its own and in association with transdermal nicotine patch.

RATIONALE: Monoamine oxidase B (MAO-B) activity is reduced in smokers. A MAO-B inhibitor alone or co-administered with nicotine may mimic the effects of smoking and be a candidate drug for smoking cessation. OBJECTIVE: This study aims to determine the efficacy and safety of EVT302, a selective reversible MAO-B inhibitor, alone and on top of nicotine patch (NP) in smoking cessation. METHODS: This was a randomised, double blind, placebo-controlled phase II, multicentre trial. Smokers (≥10 cigarettes/day) received either EVT302 (N = 145) or placebo (N = 145), or EVT302 (N = 61) or placebo (N = 61) on top of open label NP 21 mg/day for 8 weeks. The main comparison was between EVT302 and placebo without NP. The primary outcome measure was end-of-treatment 4-week continuous abstinence rate (CAR). SECONDARY OUTCOME MEASURES: point prevalence abstinence rate, saliva cotinine concentrations in the groups without NP, urge to smoke, nicotine withdrawal symptoms and assessment of subjective effects of cigarettes. RESULTS: The 4-week CAR was 15.2 % in the placebo, 17.2 % in the EVT302, 26.8 % in the NP + placebo and 32.8 % in the NP + EVT302 groups, respectively. There was no difference between EVT302 and placebo either alone (adjusted OR: 1.45, 95 % CI: 0.65-3.26) or when co-administered with NP. No statistically significant difference occurred for the secondary outcome measures. CONCLUSIONS: The selective, reversible MAO-B inhibitor EVT302 was not superior to placebo in helping smokers quit, in line with data with selegiline and confirms that MAO-B inhibitors are not effective in smoking cessation. Co-administration of NP does not provide a supplementary benefit.

Certolizumab pegol plus MTX administered every 4 weeks is effective in patients with RA who are partial responders to MTX.

OBJECTIVE: Certolizumab pegol (CZP) is known to be effective as monotherapy at a dosage of 400 mg every 4 weeks in patients with active RA who have failed DMARDs. The aim of this study was to investigate every 4-week CZP in addition to continued MTX therapy in patients with an inadequate response to MTX alone. METHODS: Patients with active RA with inadequate response to MTX, on background MTX, were randomized to double-blind treatment with CZP 400 mg or placebo every 4 weeks for 24 weeks (NCT00544154). The primary efficacy end-point was the ACR 20% improvement criteria (ACR20) response rate at Week 24. Other end-points included ACR50 and ACR70 response rates, ACR core components, 28-joint DAS (ESR) with three variables (DAS28-3) and health-related quality-of-life outcomes in addition to safety. RESULTS: Of 247 randomized patients, 126 received CZP and 121 received placebo, in addition to MTX. ACR20 response rates were 45.9 vs 22.9%, respectively [P < 0.001 analysed by the Cochran-Mantel-Haenszel (CMH) method], with improvements being apparent from Week 1. Statistically significant improvements over placebo were seen with CZP for ACR50, ACR core components, DAS28-3 and physical functioning. Rates of treatment-related adverse events were similar between groups (25.0 vs 27.7%), and there were no deaths or serious opportunistic infections. CONCLUSION: CZP 400 mg every 4 weeks plus MTX demonstrated a favourable risk-benefit profile with rapid onset of action in RA patients with an inadequate response to an earlier MTX therapy.